tbuckley/cabot-search huggingface dataset:
MesoGraph: Automatic profiling of mesothelioma subtypes from histological images
Authors: Mark Eastwood, Heba Sailem, Silviu Tudor Marc, Xiaohong Gao, Judith Offman, Emmanouil Karteris, Angeles Montero Fernandez, Danny Jonigk, William Cookson, Miriam Moffatt, Sanjay Popat, Fayyaz Minhas, Jan Lukas Robertus
Journal: Cell Reports Medicine (2023)

Mesothelioma is classified into three histological subtypes, epithelioid, sarcomatoid, and biphasic, according to the relative proportions of epithelioid and sarcomatoid tumor cells present. Current guidelines recommend that the sarcomatoid component of each mesothelioma is quantified, as a higher percentage of sarcomatoid pattern in biphasic mesothelioma shows poorer prognosis. In this work, we develop a dual-task graph neural network (GNN) architecture with ranking loss to learn a model capable of scoring regions of tissue down to cellular resolution. This allows quantitative profiling of a tumor sample according to the aggregate sarcomatoid association score. Tissue is represented by a cell graph with both cell-level morphological and regional features. We use an external multicentric test set from Mesobank, on which we demonstrate the predictive performance of our model. We additionally validate our model predictions through an analysis of the typical morphological features of cells according to their predicted score.
POS0759 MONOGENIC DISORDERS IN THE MAIDEN COHORT OF PEDIATRIC RHEUMATOLOGICAL DISEASES OF NEPAL- A SPECK OF IMPRINT ON EVEREST
Authors: D. Bhattarai, A. Banday, P. Patra, A. Neupane
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Monogenic causes are increasingly being detected in pediatric rheumatological diseases (PRDs).[<sup>1]</sup> Monogenic disorders are inborn errors of immunity resulting into innate immune disturbance and autoinflammation. With increasing awareness and diagnostics, PRDs are diagnosed with increasing frequency and accuracy in Nepal. <h3>Objectives</h3> To describe the profile of children diagnosed with PRDs and monogenic causes explored on them at a tertiary care center in Nepal during 2020-2022. <h3>Methods</h3> Case records of patients diagnosed with PRDs during Aug 2020-November 2022 were analysed. The lead author (DB) collated data from all patients. Diagnosis and treatments were based on internationally acclaimed guidelines. Genotyping was done by whole exome sequencing and/or sanger sequencing. <h3>Results</h3> The availability of subspecialists, diagnostics, and therapeutics has shifted the paradigm of PRDs in developing countries. A total of 454 patients with PRDs were diagnosed. Mean duration from initial presentation to diagnosis was 12.5 months. Juvenile idiopathic arthritis (JIA) (including systemic JIA) (n = 131), connective tissue disorders (n = 113) and vasculitides (n = 104) constituted the largest proportion of PRDs. Arthritis related to infection was observed in 42 cases whereas autoinflammatory disorders were diagnosed in 29. Monogenic causes were detected in 19 patients (<b>Table 1</b>). Majority were of non-inflammosome related conditions. Causative genes were <i>CECR1, ARPC1B, TNFAIP3, NLRP3, TNFRSF1A, MVK, PSTPIP1, NOD2, NLRP3, STX11, TNFRSF6, XIAP, BMPR2, PIK3CD, CTLA4, GATA2</i> and <i>C1QA</i>. Clinical features included recurrent fever, rashes, edema, lymphadenopathy, arthritis, vasculitis, ear and ocular issues, organomegaly, and various multisystemic symptoms. Treatment of polyarteritis nodosa with mycophenolate mofetil and idiopathic calcinosis with methotrexate and pamidronate were notable reports from our cohort. Oligoarthritis in X-linked agammaglobulinemia was a peculiar finding. One child with the monogenic PRD has undergone hematopoietic stem cell transplantation. <h3>Conclusion</h3> We present first and largest cohort of PRDs from Nepal. Noticeable number of unique monogenic causes of PRDs were diagnosed for the first time in the country. There are significant challenges in diagnosis and treatment of PRDs in resource-limited settings. Various socioeconomic and environmental factors coupled with lack of awareness, fewer referrals, and inexpedient treatment accounted for a late presentation, missed diagnosis, increased morbidity, disability, and mortality. <h3>Reference</h3> [1] Tangye SG, Al-Herz W, Bousfiha A, et al. Human Inborn Errors of Immunity: 2022 Update on the Classification from the IUIS Expert Committee. J Clin Immunol. 2022;1-35 <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> None Declared.
68Ga-PSMA PET/CT Images of Multiple Cutaneous Metastases in a Patient With Prostate Carcinoma
Authors: Ilknur Ak Sivrikoz, Hakan Deveci, Ali Murat Ak, Ersoy Acer
Journal: Clinical Nuclear Medicine (2023)

Although distant cutaneous metastasis is an uncommon presentation of prostate cancer, it remains an important diagnostic consideration as an advanced disease and a poor prognosis. Herein we present a rare case of prostate cancer patient whose multiple cutaneous metastases were treated with 177Lu-PSMA-617 radioligand treatment. To our knowledge, it is the first report in which a complete response was seen with 68Ga-PSMA PET/CT scan after 177Lu-PSMA-617 radioligand treatment.
A Phase 1, Open-label, Dose-Ascending Study to Evaluate the Safety and Tolerability of the Therapeutic Radiopharmaceutical 131I-MIP-1095 for the Treatment of Metastatic Castration-Resistant Prostate Cancer
Authors: Andrew L. Laccetti, Lisa Bodei, Joseph A. O'Donoghue, Wolfgang A. Weber, Michael J. Morris
Journal: Clinical Nuclear Medicine (2023)

131I-MIP-1095 is a targeted radiotherapeutic that contains 131I, a β-particle emitter, and MIP-1095, a urea-based ligand for prostate-specific membrane antigen. We report the first phase 1, dose-escalation study of 131I-MIP-1095 in patients with metastatic castration-resistant prostate cancer (mCRPC).This study enrolled men with mCRPC refractory to second-generation antiandrogen(s) and taxane chemotherapy. Dosimetry/biodistribution assessments were performed. Safety and tolerability were determined in subjects who qualified for therapeutic administration of 131I-MIP-1095 with maximum tolerated activity examined in a dose-ascending manner (3 + 3 design methodology). Disease outcomes including prostate-specific antigen (PSA) change, tumor response, survival, and circulating tumor cell concentration were assessed.A total of 9 subjects with mCRPC were included in this study. On the basis of dosimetry results, 5 of 9 patients were treated: 3 in cohort 1 (50 mCi) and 2 in cohort 2 (75 mCi). Accrual stopped at the cohort 2 activity level in response to the US Food and Drug Administration mandate for 131I-MIP-1095 manufacturing concerns. Parotid/salivary glands (3.5 Gy/Bq), liver (2.2 Gy/Bq), kidneys (1.3 Gy/Bq), and spleen (0.7 Gy/Bq) demonstrated the greatest extent of 131I-MIP-1095 exposure. There were no deaths, serious adverse events, or drug discontinuations due to treatment-emergent adverse events. Grade 1-2 thrombocytopenia, anemia, leukopenia, and dry mouth most commonly occurred. One subject (33.3%) exhibited maximum decline for the PSA response of 50% or greater.131I-MIP-1095 demonstrated favorable dosimetry, biodistribution, and safety, as well as a modest PSA response supporting further investigation for treatment of men with mCRPC.Clinical Trial Registration: ClinicalTrials.gov identifier: NCT03030885, Registered January 25, 2017 (https://clinicaltrials.gov/ct2/show/NCT03030885).
Comparison of 68Ga-PSMA-HBED-CC and 18F-FDG PET/CT in the Evaluation of Adenoid Cystic Carcinoma—A Prospective Study
Authors: Shamim Ahmed Shamim, Naresh Kumar, Geetanjali Arora, Deepak Kumar, Anshika Pathak, Alok Thakkar, Kapil Sikka, Chirom Amit Singh, Aanchal Kakkar, Ashu Seith Bhalla
Journal: Clinical Nuclear Medicine (2023)

18F-FDG PET/CT plays a major role in diagnosis and staging of head and neck cancer; however, FDG has lower uptake in adenoid cystic carcinoma (AdCC). Prostate-specific membrane antigen (PSMA) expression is found to be associated with endothelial cells or tumor neovasculature in malignant AdCC and salivary duct carcinoma. Thus, present study is aimed to compare the role of 68Ga-PSMA and 18F-FDG PET/CT in patients with primary and/or metastatic AdCC.Histopathologically proven AdCC patients were intravenously injected with 370 MBq (10 mCi) of 18F-FDG and 111-185 MBq (3-5 mCi) of 68Ga-PSMA. Images were acquired at 60 and 45 minutes postinjection for 18F-FDG and 68Ga-PSMA, respectively, on dedicated PET/CT scanners. Visual and semiquantitative analyses of PSMA expression in regional and metastatic sites were performed by 2 experienced nuclear medicine physicians.Seventeen patients (7 men, 10 women) having mean age of 44 ± 14.19 years were prospectively included in the study. Of 17 patients, FDG PET/CT was performed in only 14 (82%) patients. PSMA and FDG uptakes were seen at the primary site in 16 (94%) and 13 (93%) patients, respectively, whereas 1 patient was postradical tumor excision. Lung lesions (n = 7) and lymph nodes (n = 5) were detected on both FDG and PSMA PET scans. However, cerebellar and meningeal metastasis (n = 1, 6%) and bony lesions (n = 2, 12%) were detected only on PSMA PET/CT but not visualized on FDG PET/CT scan.PSMA may have theranostic importance in unresectable or metastatic AdCC, besides having a role in staging/restaging.
Climate change and cancer: the Environmental Justice perspective
Authors: Leticia M Nogueira, K Robin Yabroff
Journal: JNCI Journal of the National Cancer Institute (2023)

Abstract Despite advances in cancer control—prevention, screening, diagnosis, treatment, and survivorship—racial disparities in cancer incidence and survival persist and, in some cases, are widening in the United States. Since 2020, there’s been growing recognition of the role of structural racism, including structurally racist policies and practices, as the main factor contributing to historical and contemporary disparities. Structurally racist policies and practices have been present since the genesis of the United States and are also at the root of environmental injustices, which result in disproportionately high exposure to environmental hazards among communities targeted for marginalization, increased cancer risk, disruptions in access to care, and worsening health outcomes. In addition to widening cancer disparities, environmental injustices enable the development of polluting infrastructure, which contribute to detrimental health outcomes in the entire population, and to climate change, the most pressing public health challenge of our time. In this commentary, we describe the connections between climate change and cancer through an Environmental Justice perspective (defined as the fair treatment and meaningful involvement of people of all racialized groups, nationalities, or income, in all aspects, including development, implementation, and enforcement, of policies and practices that affect the environment and public health), highlighting how the expertise developed in communities targeted for marginalization is crucial for addressing health disparities, tackling climate change, and advancing cancer control efforts for the entire population.
Psychoanalysis
Journal: JAMA (2023)

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Diagnosis and Treatment of Bipolar Disorder
Authors: Andrew A. Nierenberg, Bruno Agustini, Ole Köhler-Forsberg, Cristina Cusin, Douglas Katz, Louisa G. Sylvia, Amy Peters, Michael Berk
Journal: JAMA (2023)

Importance Bipolar disorder affects approximately 8 million adults in the US and approximately 40 million individuals worldwide. Observations Bipolar disorder is characterized by recurrent episodes of depression and mania or hypomania. Bipolar depressive episodes are similar to major depressive episodes. Manic and hypomanic episodes are characterized by a distinct change in mood and behavior during discrete time periods. The age of onset is usually between 15 and 25 years, and depression is the most frequent initial presentation. Approximately 75% of symptomatic time consists of depressive episodes or symptoms. Early diagnosis and treatment are associated with a more favorable prognosis. Diagnosis and optimal treatment are often delayed by a mean of approximately 9 years following an initial depressive episode. Long-term treatment consists of mood stabilizers, such as lithium, valproate, and lamotrigine. Antipsychotic agents, such as quetiapine, aripiprazole, asenapine, lurasidone, and cariprazine, are recommended, but some are associated with weight gain. Antidepressants are not recommended as monotherapy. More than 50% of patients with bipolar disorder are not adherent to treatment. Life expectancy is reduced by approximately 12 to 14 years in people with bipolar disorder, with a 1.6-fold to 2-fold increase in cardiovascular mortality occurring a mean of 17 years earlier compared with the general population. Prevalence rates of metabolic syndrome (37%), obesity (21%), cigarette smoking (45%), and type 2 diabetes (14%) are higher among people with bipolar disorder, contributing to the risk of early mortality. The annual suicide rate is approximately 0.9% among individuals with bipolar disorder, compared with 0.014% in the general population. Approximately 15% to 20% of people with bipolar disorder die by suicide. Conclusions and Relevance Bipolar disorder affects approximately 8 million adults in the US. First-line therapy includes mood stabilizers, such as lithium, anticonvulsants, such as valproate and lamotrigine, and atypical antipsychotic drugs, such as quetiapine, aripiprazole, asenapine, lurasidone, and cariprazine.
Intraventricular Lavage vs External Ventricular Drainage for Intraventricular Hemorrhage
Authors: Mette Haldrup, Mads Rasmussen, Niwar Mohamad, Stig Dyrskog, Line Thorup, Nikola Mikic, Joakim Wismann, Mads Grønhøj, Frantz Rom Poulsen, Mojtaba Nazari, Naveed Ur Rehman, Claus Ziegler Simonsen, Anders Rosendal Korshøj
Journal: JAMA Network Open (2023)

Importance Intraventricular lavage has been proposed as a minimally invasive method to evacuate intraventricular hemorrhage. There is little evidence to support its use. Objective To evaluate the safety and potential efficacy of intraventricular lavage treatment of intraventricular hemorrhage. Design, Setting, and Participants This single-blinded, controlled, investigator-initiated 1:1 randomized clinical trial was conducted at Aarhus University Hospital and Odense University Hospital in Denmark from January 13, 2022, to November 24, 2022. Follow-up duration was 90 days. The trial was set to include 58 patients with intraventricular hemorrhage. Prespecified interim analysis was performed for the first 20 participants. Data were analyzed from February to April 2023. Interventions Participants were randomized to receive either intraventricular lavage or standard drainage. Main Outcomes and Measures The main outcome was risk of catheter occlusions. Additional safety outcomes were catheter-related infections and procedure time, length of stay at the intensive care unit, duration of treatment, and 30-day mortality. The main outcome of the prespecified interim analysis was risk of severe adverse events. Efficacy outcomes were hematoma clearance, functional outcome, overall survival, and shunt dependency. Results A total of 21 participants (median [IQR] age, 67 [59-82] years; 14 [66%] male) were enrolled, with 11 participants randomized to intraventricular lavage and 10 participants randomized to standard drainage; 20 participants (95%) had secondary intraventricular hemorrhage. The median (IQR) Graeb score was 9 (5-11), and the median (IQR) Glasgow Coma Scale score was 6.5 (4-8). The study was terminated early due to a significantly increased risk of severe adverse events associated with intraventricular lavage at interim analysis (risk difference for control vs intervention, 0.43; 95% CI, 0.06-0.81; P = .04; incidence rate ratio for control vs intervention, 6.0; 95% CI, 1.38-26.1; P = .01). The rate of catheter occlusion was higher for intraventricular lavage compared with drainage (6 of 16 patients [38%] vs 2 of 13 patients [7%]; hazard ratio, 4.4 [95% CI, 0.6-31.2]; P = .14), which met the prespecified α = .20 level. Median (IQR) procedure time for catheter placement was 53.5 (33-75) minutes for intraventricular lavage vs 12 (4-20) minutes for control ( P &amp;amp;lt; .001). Conclusions and Relevance This randomized clinical trial of intraventricular lavage vs standard drainage found that intraventricular lavage was encumbered with a significantly increased number of severe adverse events. Caution is recommended when using the device to ensure patient safety. Trial Registration ClinicalTrials.gov Identifier: NCT05204849
Computer-Supervised EVD Raises Safety Questions in ICU Care of IVH
Authors: Daniel F. Hanley, Wendy C. Ziai, Issam A. Awad
Journal: JAMA Network Open (2023)

Mette Haldrup, MD; Mads Rasmussen, MD, PhD; Niwar Mohamad, MD; Stig Dyrskog, MD, PhD; Line Thorup, MD; Nikola Mikic, MD; Joakim Wismann, MD; Mads Grønhøj, MD, PhD; Frantz Rom Poulsen, MD, PhD; Mojtaba Nazari, MSc; Naveed Ur Rehman, MSc, PhD; Claus Ziegler Simonsen, MD, PhD; Anders Rosendal Korshøj, MD, PhD
Antenatal Screening for <i>CFTR</i> Variants
Authors: Nikolaos Vlachadis, Nikolaos Vrachnis
Journal: JAMA (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
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Journal: JAMA Network Open (2023)

Alissa Bernstein Sideman, PhD, MPH, MA; Melissa Ma, BA; Alma Hernandez de Jesus, BA; Cecilia Alagappan, RN; Na’amah Razon, MD, PhD; Daniel Dohan, PhD; Anna Chodos, MD, MPH; Tala Al-Rousan, MD, MPH; Loren I. Alving, MD; Freddi Segal-Gidan, PA, PhD; Howie Rosen, MD; Katherine P. Rankin, PhD; Katherine L. Possin, PhD; Soo Borson, MD
Microbial-host-isozyme: unveiling a new era in microbiome–host interaction
Authors: Lei Miao, Herbert Tilg, Ming-Hua Zheng
Journal: Gut Microbes (2023)

Wang K. et al. introduced the concept of Microbial-Host isozymes (MHIs) and highlighted their role in mediating microbiota–host interactions. They identified bacterial-derived DPP4 as an isoenzyme affecting glucose tolerance and showed that host DPP4 inhibitors may not effectively target bacterial DPP4. They developed an MHI screen system, identifying 71 MHIs in healthy gut microbiota. Among them, DPP4 isozymes degrade GLP-1, explaining variable responses to sitagliptin. This breakthrough opens new avenues for metabolic disorder treatment. However, the complex nature of gut symbiotic bacteria requires further research to understand MHI mechanisms, regulatory roles, and interactions with the host. Precise interventions in gut microbiota offer personalized approaches to metabolic diseases.
Magnetic resonance imaging of pancreatic islets using tissue–adhesive particles containing iron oxide nanoparticles
Authors: Phuong Le Tran, Tung Thanh Pham, Han Sin Lee, Soojung Hahn, Jeong Uk Choi, Jae Hyeon Kim, Hu-Lin Jiang, Simmyung Yook, Jee-Heon Jeong
Journal: Journal of Controlled Release (2023)
Organ Procurement Using Normothermic Regional Perfusion
Authors: Kari Esbensen, Kenneth Prager
Journal: JAMA (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal